(2R,4S,5R,6R)-5-acetamido-2-[4-[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methylcarbamoyl]triazol-1-yl]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid | 1452840-40-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: (2R,4S,5R,6R)-5-acetamido-2-[4-[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methylcarbamoyl]triazol-1-yl]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid
• CAS: 1452840-40-2
• 化学式: C₂₃H₃₂N₈O₁₃
• 分子量: 628.553
• InChiKey: QZBNLLRGLXWZFZ-HYGYQVPNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  325
• 氢给体数：
  10
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  2',3'-O-isopropylidene N4-acetylcytidine 在 吡啶 、 sodium azide 、 copper(ll) sulfate pentahydrate 、 palladium on activated charcoal 、 sodium methylate 、 1-羟基苯并三唑 、 甲基磺酰氯 、 sodium ascorbate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氘代甲醇-d 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 75.0h， 生成 (2R,4S,5R,6R)-5-acetamido-2-[4-[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methylcarbamoyl]triazol-1-yl]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid
  参考文献：
  名称：

  Sialyltransferase inhibitors: consideration of molecular shape and charge/hydrophobic interactions

  摘要：

  In order to evaluate the importance of molecular shape of inhibitor molecules and the charge/H-bond and hydrophobic interactions, we synthesized three types of molecules and tested them against a sialyltransferase. The first type of compounds were designed as substrate mimics in which the phosphate in CMP-Neu5NAc was replaced by a non-hydrolysable, uncharged 1,2,3-triazole moiety. The second type of compound contained a 2-deoxy-2,3-dehydro-acetylneuraminic moiety which was linked to cytidine through its carboxylic acid and amide linkers. In the third type of compound the sialyl phosphate was substituted by an aryl sulfonamide which was then linked to cytidine. Inhibition study of these cytidine conjugates against Campylobacter jejuni sialyltransferase Cst 06 showed that the first type of molecules are competitive inhibitors, whereas the other two could only inhibit the enzyme non-competitively. The results indicate that although the binding specificity may be guided by molecular shape and H-bond interaction, the charge and hydrophobic interactions contributed most to the binding affinity. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2012.12.017

文献信息

• Sialyltransferase inhibitors: consideration of molecular shape and charge/hydrophobic interactions
  作者：Rishi Kumar、Ravindranath Nasi、Milan Bhasin、Nam Huan Khieu、Margaret Hsieh、Michel Gilbert、Harold Jarrell、Wei Zou、Harold J. Jennings

  DOI：10.1016/j.carres.2012.12.017

  日期：2013.8

  In order to evaluate the importance of molecular shape of inhibitor molecules and the charge/H-bond and hydrophobic interactions, we synthesized three types of molecules and tested them against a sialyltransferase. The first type of compounds were designed as substrate mimics in which the phosphate in CMP-Neu5NAc was replaced by a non-hydrolysable, uncharged 1,2,3-triazole moiety. The second type of compound contained a 2-deoxy-2,3-dehydro-acetylneuraminic moiety which was linked to cytidine through its carboxylic acid and amide linkers. In the third type of compound the sialyl phosphate was substituted by an aryl sulfonamide which was then linked to cytidine. Inhibition study of these cytidine conjugates against Campylobacter jejuni sialyltransferase Cst 06 showed that the first type of molecules are competitive inhibitors, whereas the other two could only inhibit the enzyme non-competitively. The results indicate that although the binding specificity may be guided by molecular shape and H-bond interaction, the charge and hydrophobic interactions contributed most to the binding affinity. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.